tbuckley/cabot-search huggingface dataset:
Is antibiotic prophylaxis generally safe and effective in surgical and nonsurgical scenarios? Evidence from an umbrella review of randomized controlled trials
Authors: Linhu Liu, Zhongyu Jian, Menghua Wang, Chi Yuan, Ya Li, Yucheng Ma, Xi Jin, Hong Li, Yazhou He, Changhai Liu, Sheyu Li, Kunjie Wang
Journal: International Journal of Surgery (2023)

Background: We aimed to comprehensively evaluate the efficacy and safety of antibiotic prophylaxis through surgical and non-surgical scenarios and assess the strength of evidence. Materials and Methods: We performed an umbrella review of meta-analyses of randomized controlled trials (RCTs). An evidence map was created to summarize the absolute benefits of antibiotic prophylaxis in each scenario and certainty of evidence. Results: 75 meta-analyses proved eligible with 725 RCTs and 78 clinical scenarios in surgical and medical prophylaxis. Of 119 health outcomes, 67 (56.3%) showed statistically significant benefits, 34 of which were supported by convincing or highly suggestive evidence from RCTs. For surgeries, antibiotic prophylaxis may minimize infection occurrences in most surgeries except Mohs surgery, simple hand surgery, herniorrhaphy surgery, hepatectomy, thyroid surgery, rhinoplasty, stented distal hypospadias repair, midurethral sling placement, endoscopic sinus surgery, and transurethral resection of bladder tumors with only low to very low certainty evidence. For non-surgery invasive procedures, only low to very low certainty evidence showed benefits of antibiotic prophylaxis for cystoscopy, postoperative urinary catheterization, and urodynamic study. For medical prophylaxis, antibiotic prophylaxis showed greater benefits in non-emergency scenarios, in which patients were mainly with weakened immune systems, or at risk of recurrent chronic infections. Antibiotics prophylaxis may increase antibiotic resistance or other adverse events in most scenarios and reached significance in cystoscopy, afebrile neutropenia following chemotherapy and hematopoietic stem cell transplantation. Conclusions: Antibiotic prophylaxis in surgical and non-surgical scenarios is generally effective and seems independent of surgical cleanliness and urgency of diseases. Its safety is not well determined due to lack of available data. Nevertheless, the low quality of current evidence limits the external validity of these findings, necessitating clinicians to judiciously assess indications, balancing low infection rates with antibiotic-related side effects.
Risk of congestive heart failure and mortality following lymphovenous anastomosis: a nationwide population-based retrospective cohort study
Authors: Joon Seok Lee, Hyun Su Kang, Jae-Ho Chung, Jeong Yeop Ryu
Journal: International Journal of Surgery (2023)

Background: Lymphovenous anastomosis (LVA) enables lymphatic fluid to drain into the venous system. However, no study has investigated the association between LVA and heart failure (HF) caused by fluid overload in the blood circulating system. The purpose of our study was to determine whether LVA increases the risk of HF and mortality. Material and methods: This nationwide retrospective study evaluated a total of 1400 lymphedema patients who underwent LVA and two control cohorts with 28 000 lymphedema who did not undergo LVA and 70 000 age-matched and sex-matched participants from the Korean National Health Insurance database were included. Blood pressure, body mass index (BMI), glucose and cholesterol levels, smoking history, and comorbidities were obtained during National Health Insurance Service – Health Screening (NHIS-HealS). The incidence, adjusted risk for HF, and mortality were evaluated. Results: Adjusted HRs for HF were 1.20 (confidence interval [CI], 1.03–1.40) and 1.30 (CI, 1.12–1.50), referenced by the general population control cohort and patients with lymphedema without LVA, respectively. In age, sex, BMI, and smoking status-stratified analyses, heightened risk of HF was evident across all sexes, spanning both young and old age groups, encompassing individuals with various smoking statuses, and those with a BMI of 18.5 or higher. Among these groups, the risk was notably greater in males compared to females, higher in younger individuals as opposed to older ones, and further elevated within the BMI range of 18.5–25. Conclusions: LVA is associated with an increased HF risk, independent of cardiovascular risk factors and associated comorbidities. This association is prominent in participants aged &lt;50 years, in males, and in the normal-to-obese (BMI ≥18.5 kg/m 2 ) group. Among patients with lymphedema, LVA did not significantly affect mortality.
Diagnosis and investigation of suspected haemophagocytic lymphohistiocytosis in adults: 2023 Hyperinflammation and HLH Across Speciality Collaboration (HiHASC) consensus guideline
Authors: Miriam F Cox, Strachan Mackenzie, Ryan Low, Michael Brown, Emilie Sanchez, Aisling Carr, Ben Carpenter, Mark Bishton, Andrew Duncombe, Akpabio Akpabio, Austin Kulasekararaj, Fang En Sin, Alexis Jones, Akhila Kavirayani, Ethan S Sen, Vanessa Quick, Gurdeep S Dulay, Sam Clark, Kris Bauchmuller, Rachel S Tattersall, Jessica J Manson
Journal: The Lancet Rheumatology (2023)
Engineered exosomes-based theranostic strategy for tumor metastasis and recurrence
Authors: Min Deng, Shuang Wu, Peizheng Huang, Yun Liu, Chong Li, Ji Zheng
Journal: Asian Journal of Pharmaceutical Sciences (2023)

Metastasis-associated processes are the predominant instigator of fatalities linked to cancer, wherein the pivotal role of circulating tumor cells lies in the resurgence of malignant growth. In recent epochs, exosomes, constituents of the extracellular vesicle cohort, have garnered attention within the field of tumor theranostics owing to their inherent attributes encompassing biocompatibility, modifiability, payload capacity, stability, and therapeutic suitability. Nonetheless, the rudimentary functionalities and limited efficacy of unmodified exosomes curtail their prospective utility. In an effort to surmount these shortcomings, intricate methodologies amalgamating nanotechnology with genetic manipulation, chemotherapy, immunotherapy, and optical intervention present themselves as enhanced avenues to surveil and intercede in tumor metastasis and relapse. This review delves into the manifold techniques currently employed to engineer exosomes, with a specific focus on elucidating the interplay between exosomes and the metastatic cascade, alongside the implementation of tailored exosomes in abating tumor metastasis and recurrence. This review not only advances comprehension of the evolving landscape within this domain but also steers the trajectory of forthcoming investigations.
Protective efficacy of short-term infection with Necator americanus hookworm larvae in healthy volunteers in the Netherlands: a single-centre, placebo-controlled, randomised, controlled, phase 1 trial
Authors: Marie-Astrid Hoogerwerf, Jacqueline J Janse, Vincent P Kuiper, Roos van Schuijlenburg, Yvonne CM Kruize, Jeroen C Sijtsma, Beckley A Nosoh, Jan-Pieter R Koopman, Petra H Verbeek-Menken, Inge M Westra, Pauline Meij, Eric AT Brienen, Leo G Visser, Lisette van Lieshout, Simon P Jochems, Maria Yazdanbakhsh, Meta Roestenberg
Journal: The Lancet Microbe (2023)

BackgroundVaccine development against hookworm is hampered by the absence of the development of protective immunity in populations repeatedly exposed to hookworm, limiting identification of mechanisms of protective immunity and new vaccine targets. Immunisation with attenuated larvae has proven effective in dogs and partial immunity has been achieved using an irradiated larvae model in healthy volunteers. We aimed to investigate the protective efficacy of immunisation with short-term larval infection against hookworm challenge.MethodsWe did a single-centre, placebo-controlled, randomised, controlled, phase 1 trial at Leiden University Medical Center (Leiden, Netherlands). Healthy volunteers (aged 18–45 years) were recruited using advertisements on social media and in publicly accessible areas. Volunteers were randomly assigned (2:1) to receive three short-term infections with 50 infectious Necator americanus third-stage filariform larvae (50L3) or placebo. Infection was abrogated with a 3-day course of albendazole 400 mg, 2 weeks after each exposure. Subsequently all volunteers were challenged with two doses of 50L3 at a 2-week interval. The primary endpoint was egg load (geometric mean per g faeces) measured weekly between weeks 12 and 16 after first challenge, assessed in the per-protocol population, which included all randomly assigned volunteers with available data on egg counts at week 12–16 after challenge. This study is registered with ClinicalTrials.gov, NCT03702530.FindingsBetween Nov 8 and Dec 14, 2018, 26 volunteers were screened, of whom 23 enrolled in the trial. The first immunisation was conducted on Dec 18, 2018. 23 volunteers were randomly assigned (15 to the intervention group and eight to the placebo group). Egg load after challenge was lower in the intervention group than the placebo group (geometric mean 571 eggs per g [range 372–992] vs 873 eggs per g [268–1484]); however, this difference was not statistically significant (p=0·10). Five volunteers in the intervention group developed a severe skin rash, which was associated with 40% reduction in egg counts after challenge (geometric mean 742 eggs per g [range 268–1484] vs 441 eggs per g [range 380–520] after challenge; p=0·0025) and associated with higher peak IgG1 titres.InterpretationTo our knowledge, this is the first study to describe a protective effect of short-term exposure to hookworm larvae and show an association with skin response, eosinophilic response, and IgG1. These findings could inform future hookworm vaccine development.FundingDioraphte Foundation.
Cognitive performance following stroke, transient ischaemic attack, myocardial infarction, and hospitalisation: an individual participant data meta-analysis of six randomised controlled trials
Authors: Laura Sherlock, Shun Fu Lee, Aristeidis H Katsanos, Tali Cukierman-Yaffe, Michelle Canavan, Raed Joundi, Mukul Sharma, Ashkan Shoamanesh, Carol Brayne, Hertzel C Gerstein, Martin J O’Donnell, Graciela Muniz-Terrera, Salim Yusuf, Jackie Bosch, William N Whiteley
Journal: The Lancet Healthy Longevity (2023)

BackgroundSurvivors of stroke are often concerned about cognitive problems, and information on the risk of cognitive problems often comes from small studies. We aimed to estimate years of cognitive ageing associated with stroke compared with transient ischaemic attack, myocardial infarction, and other hospitalisations in a large population.MethodsUsing data from six randomised controlled trials (ORIGIN, ONTARGET, TRANSCEND, COMPASS, HOPE-3, and NAVIGATE ESUS), we completed an individual participant data meta-analysis using data requested from the Public Health Research Institute to estimate the association of stroke (by type and severity), transient ischaemic attack, myocardial infarction, and other hospitalisations with cognitive performance measured at the end of each trial. We included participants in any of these randomised controlled trials with a cognitive assessment at baseline and at least one other timepoint. Cognitive performance was measured with the Mini-Mental State Examination or the Montreal Cognitive Assessment, transformed into Z scores. We estimated Z score differences in end of trial cognitive performance between people with and without events and calculated corresponding years of cognitive ageing in these trials, and additionally calculated using a population representative cohort—the Cognitive Function and Ageing Study.FindingsIn 64 106 participants from 55 countries, compared with no event, stroke was associated with 18 years of cognitive ageing (1487 strokes included in the model, 95% CI 10 to 28; p<0·0001) and transient ischaemic attack with 3 years (660 transient ischaemic attacks included in the model, 0 to 6; p=0·021). Myocardial infarction (p=0·60) and other hospitalisations (p=0·26) were not associated with cognitive ageing. The mean difference in SD compared with people without an event was –0·84 (95% CI –0·91 to –0·76; p<0·0001) for disabling stroke, and –0·12 (–0·19 to –0·05; p=0·0012) for non-disabling stroke. Haemorrhagic stroke was associated with worse cognition (–0·75, –0·95 to –0·55; p<0·0001) than ischaemic stroke (–0·42, –0·48 to –0·36; p <0·0001).InterpretationStroke has a substantial effect on cognition. The effects of transient ischaemic attack were small, whereas myocardial infarction and hospitalisation had a neutral effect. Prevention of stroke could lead to a reduction in cognitive ageing in those at greatest risk.FundingPopulation Health Research Institute and Chief Scientist Office of Scotland.
The global burden of fracture-related infection: can we do better?
Authors: Willem-Jan Metsemakers, T Fintan Moriarty, Mario Morgenstern, Leonard Marais, Jolien Onsea, Robert V O'Toole, Melissa Depypere, William T Obremskey, Michael H J Verhofstad, Martin McNally, Saam Morshed, Marjan Wouthuyzen-Bakker, Charalampos Zalavras
Journal: The Lancet Infectious Diseases (2023)
Polio eradication, elusive but achievable
Authors: None The Lancet Microbe
Journal: The Lancet Microbe (2023)

World Polio Day 2023, on Oct 24, offered the Global Polio Eradication Initiative (GPEI) and other supporters of the cause an opportunity to reinvigorate their global call to "Make Polio History". Since GPEI's launch in 1988, when poliomyelitis (polio) paralysed over 350 000 children every year, remarkable progress has been made in the fight against the disease: wild poliovirus cases have decreased by more than 99% and wild poliovirus types 2 and 3 have been declared eradicated. However, GPEI's original aim to end polio by the year 2000 was not met, and almost a quarter of a century on, this aim still appears elusive with two substantial challenges needing to be addressed.
Effect of implementation strategies on pre-exposure prophylaxis persistence among female sex workers in South Africa: an interrupted time series study
Authors: Amrita Rao, Hlengiwe Mhlophe, Anje Pretorius, Mfezi Mcingana, Jennifer Mcloughlin, Lillian Shipp, Stefan Baral, Harry Hausler, Sheree Schwartz, Catherine Lesko
Journal: The Lancet HIV (2023)
Age disparities in glucose-lowering treatment for Danish people with type 2 diabetes: a cross-sectional study between 2019 and 2020
Authors: Karl Sebastian Johansson, Cille Bülow, Espen Jimenez-Solem, Tonny Studsgaard Petersen, Mikkel Bring Christensen
Journal: The Lancet Healthy Longevity (2023)

The pharmacotherapeutic guidelines for type 2 diabetes have changed considerably during the past decades. SGLT2 inhibitors and GLP-1 receptor agonists have emerged as first-line agents by preventing cardiovascular events within a few years of treatment. In contrast, sulphonylureas and insulin have been deprioritised due to less beneficial effects and the risk of hypoglycaemia—particularly in older people who are frail. We hypothesised that medications with a high risk of hypoglycaemia were used more often in older people compared with younger people. In a nationwide cohort of people with type 2 diabetes in Denmark from 2019 to 2020, we described the use of specific glucose-lowering medications in relation to age and glycated haemoglobin A1C (HbA1c) by descriptive statistics and regression models adjusted for sex, socioeconomic factors, renal function, and several comorbidities. Among 290 890 people with type 2 diabetes, glucose-lowering medication usage peaked at age 70 years. Increasing age was associated with relatively less use of metformin, GLP-1 receptor agonists, and SGLT2 inhibitors and more use of basal insulin, DDP-4 inhibitors, and sulphonylureas. When comparing 80-year-olds with 60-year-olds at similar HbA1c levels of 6·5% (48 mmol/mol), 80-year-olds used 8% (95% CI 7–10%) fewer glucose-lowering medications, were 55% less likely to receive GLP-1 receptor agonists or SGLT2 inhibitors (relative ratio 0·45, 95% CI 0·42–0·48), and 65% more likely to receive sulphonylureas (1·65, 1·54–1·76). Among 23 032 individuals aged 80 years or older with HbA1c levels of less than 6·5% (<48 mmol/mol), 2291 (10%) used sulphonylureas or insulin. In Danish people with type 2 diabetes, the likelihood of using glucose-lowering medications with a high risk of hypoglycaemia (eg, sulphonylureas and basal insulin) increased with age, whereas the likelihood of using GLP-1 receptor agonists and SGLT2 inhibitors decreased. Some people aged 80 years or older with an HbA1c level of less than 6·5% (48 mmol/mol) were potentially overtreated with sulphonylureas or insulin. These findings emphasise the importance of frequently re-evaluating glucose-lowering treatments. None. For the Danish translation of the abstract see Supplementary Materials section.
HIV pre-exposure prophylaxis and its implementation in the PrEP Impact Trial in England: a pragmatic health technology assessment
Authors: Ann K Sullivan, John Saunders, Monica Desai, Andrea Cartier, Holly D Mitchell, Sajjida Jaffer, Dana Ogaz, Chiara Chiavenna, Andre Charlett, Victor Diamente, Rainer Golombek, Kaveh Manavi, Cecilia Priestley, Laura J Waters, Ana Milinkovic, Alan McOwan, Claudia Estcourt, Caroline A Sabin, Alison Rodger, Deborah Gold, Brian G Gazzard, Sheena McCormack, O Noel Gill
Journal: The Lancet HIV (2023)

HIV pre-exposure prophylaxis (PrEP) is highly effective in preventing HIV acquisition. To enable routine commissioning of PrEP in England, we aimed to establish population need, duration of need, PrEP uptake, and duration of use in attendees of sexual health services (SHS) in England.
Frailty and long-term survival among patients in Australian intensive care units with metastatic cancer (FRAIL-CANCER study): a retrospective registry-based cohort study
Authors: Muhammad Alamgeer, Ryan Ruiyang Ling, Ryo Ueno, Krishnaswamy Sundararajan, Raghav Sundar, David Pilcher, Ashwin Subramaniam
Journal: The Lancet Healthy Longevity (2023)

Recent advances in cancer therapeutics have improved outcomes, resulting in increasing candidacy of patients with metastatic cancer being admitted to intensive care units (ICUs). A large proportion of patients also have frailty, predisposing them to poor outcomes, yet the literature reporting on this is scarce. We aimed to assess the impact of frailty on survival in patients with metastatic cancer admitted to the ICU. In this retrospective registry-based cohort study, we used data from the Australia and New Zealand Intensive Care Society Adult Patient (age ≥16 years) database to identify patients with advanced (solid and haematological cancer) and a documented Clinical Frailty scale (CFS) admitted to 166 Australian ICUs. Patients without metastatic cancer were excluded. We analysed the effect of frailty (CFS 5–8) on long-term survival, and how this effect changed in specific subgroups (cancer subtypes, age [<65 years or ≥65 years], and those who survived hospitalisation). Because estimates tend to cluster within centres and vary between them, we used Cox proportional hazards regression models with robust sandwich variance estimators to assess the effect of frailty on survival time up to 4 years after ICU admission between groups. Between Jan 1, 2018, and March 31, 2022, 30 026 patients were eligible, and after exclusions 21 174 patients were included in the analysis; of these, 6806 (32·1%) had frailty, and 11 662 (55·1%) were male, 9489 (44·8%) were female, and 23 (0·1%) were intersex or self-reported indeterminate sex. The overall survival was lower for patients with frailty at 4 years compared with patients without frailty (29·5% vs 10·9%; p<0·0001). Frailty was associated with shorter 4-year survival times (adjusted hazard ratio 1·52 [95% CI 1·43–1·60]), and this effect was seen across all cancer subtypes. Frailty was associated with shorter survival times in patients younger than 65 years (1·66 [1·51–1·83]) and aged 65 years or older (1·40 [1·38–1·56]), but its effects were larger in patients younger than 65 years (pinteraction<0·0001). Frailty was also associated with shorter survival times in patients who survived hospitalisation (1·49 [1·40–1·59]). In patients with metastatic cancer admitted to the ICU, frailty was associated with poorer long-term survival. Patients with frailty might benefit from a goal-concordant time-limited trial in the ICU and will need suitable post-intensive care supportive management. None.
Low-dose CT screening among never-smokers with or without a family history of lung cancer in Taiwan: a prospective cohort study
Authors: Gee-Chen Chang, Chao-Hua Chiu, Chong-Jen Yu, Yeun-Chung Chang, Ya-Hsuan Chang, Kuo-Hsuan Hsu, Yu-Chung Wu, Chih-Yi Chen, Hsian-He Hsu, Ming-Ting Wu, Cheng-Ta Yang, Inn-Wen Chong, Yu-Ching Lin, Te-Chun Hsia, Meng-Chih Lin, Wu-Chou Su, Chih-Bin Lin, Kang-Yun Lee, Yu-Feng Wei, Gong-Yau Lan, Wing P Chan, Kao-Lun Wang, Mei-Han Wu, Hao-Hung Tsai, Chih-Feng Chian, Ruay-Sheng Lai, Jin-Yuan Shih, Chi-Liang Wang, Jui-Sheng Hsu, Kun-Chieh Chen, Chun-Ku Chen, Jiun-Yi Hsia, Chung-Kan Peng, En-Kuei Tang, Chia-Lin Hsu, Teh-Ying Chou, Wei-Chih Shen, Ying-Huang Tsai, Chun-Ming Tsai, Yuh-Min Chen, Yu-Chin Lee, Hsuan-Yu Chen, Sung-Liang Yu, Chien-Jen Chen, Yung-Liang Wan, Chao Agnes Hsiung, Pan-Chyr Yang, Chang-Chuan Chan, Si-Wa Chan, I-Shou Chang, Jer-Hwa Chang, Kun-San Chao, Chi-Jen Chen, Huei-Wen Chen, Chun-Ju Chiang, Hung-Yi Chiou, Mei-Chun Chou, Chi-Li Chung, Ta-Jung Chung, Yue Leon Guo, Chin-Fu Hsiao, Chien-Sheng Huang, Sheung-Fat Ko, Mei-Hsuan Lee, Yao-Jen Li, Yu-San Liao, Yueh-Hsun Lu, Hsin-You Ou, Ping-An Wu, Hwai-I Yang, Shi-Yi Yang, Szu-Chun Yang
Journal: The Lancet Respiratory Medicine (2023)
Tumor hypoxia and radiotherapy: A major driver of resistance even for novel radiotherapy modalities
Authors: Claire Beckers, Martin Pruschy, Irene Vetrugno
Journal: Seminars in Cancer Biology (2023)

Hypoxia in solid tumors is an important predictor of poor clinical outcome to radiotherapy. Both physicochemical and biological processes contribute to a reduced sensitivity of hypoxic tumor cells to ionizing radiation and hypoxia-related treatment resistances. A conventional low-dose fractionated radiotherapy regimen exploits iterative reoxygenation in between the individual fractions, nevertheless tumor hypoxia still remains a major hurdle for successful treatment outcome. The technological advances achieved in image guidance and highly conformal dose delivery make it nowadays possible to prescribe larger doses to the tumor as part of single high-dose or hypofractionated radiotherapy, while keeping an acceptable level of normal tissue complication in the co-irradiated organs at risk. However, we insufficiently understand the impact of tumor hypoxia to single high-doses of RT and hypofractionated RT. So called FLASH radiotherapy, which delivers ionizing radiation at ultra-high dose rates (> 40 Gy/sec), has recently emerged as an important breakthrough in the radiotherapy field to reduce normal tissue toxicity compared to irradiation at conventional dose rates (few Gy/min). Not surprisingly, oxygen consumption and tumor hypoxia also seem to play an intriguing role for FLASH radiotherapy. Here we will discuss the role of tumor hypoxia for radiotherapy in general and in the context of novel radiotherapy treatment approaches.